Translational crossroads for biomarkers.

A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute-supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.     

An effect of triazolam on visual attention and information processing

This study explored whether benzodiazepines selectively affect aspects of attention and/or visual information processing, as they do memory. A cued visual-search paradigm was employed, using normal volunteers and a single dose of triazolam. This paradigm provided for a detailed examination of two aspects of visual attention and information processing: 1) controlled versus automatic attention allocation (via central and peripheral cues), and 2) the extent to which processing an item in a non-cued location affects performance (via cue-validity). Triazolam, compared to placebo, significantly increased response time, and Drug Condition interacted with Cue-Validity but not Cue-Type. Based on these data, we argue that triazolam doesnot affect attention allocation butdoes affect attentional disengagement and/or attention switching mechanisms.     

Burns from electric fire-guards.

Nine children with burns caused by contact with electric fire-guards are presented. A method of preventing such injuries is recommended.     

Balance and recovery from a perturbation are impaired in people with functional ankle instability.

OBJECTIVE: To determine if differences in balance and recovery would be found between controls and participants with unilateral or bilateral functional ankle instability (FAI). DESIGN: Cross-Sectional Study. SETTING: University laboratory and Community premises. PARTICIPANTS: Twenty healthy participants(C), 19 participants with unilateral FAI [both the uninjured (UC) and unstable ankle (UI) were included] and 22 participants with bilateral FAI (BI). MAIN OUTCOME MEASURES: Balance was measured in single leg stance as: number of part foot lifts in 30 s; magnitude of medio-lateral ankle movement in two foot positions; and ability to balance on the ball of the foot. Recovery was determined by time to return to baseline medio-lateral ankle movement after a 15 degree inversion perturbation. RESULTS: The controls lifted the foot fewer times than the other three groups [C = 12.7 +/- 1.8 (mean +/- SE) foot lifts, UC = 22.9 +/- 2.5, UI = 25.1 +/- 2.3, and BI = 21.1 +/- 2.2, t-test, P = 0.006] and recovered significantly faster than the unstable ankles [C = 1.53 +/- 0.42 sec (median +/- SE), UI = 2.34 +/- 0.30 sec, BI = 2.15 +/- 0.70 sec, P < 0.02]. With FAI measured by the Cumberland Ankle Instability Tool, the external control group balanced on demi-pointe better than both instability groups (P < 0.05), and recovered quicker than all groups. CONCLUSION: There are differences in balance and recovery between external controls and participants with both unilateral and bilateral FAI but not between the legs of participants with unilateral FAI.     

Das kleinzellige Bronchialkarzinom – neue Entwicklungen nach ASCO 2007

Wiener Medizinische Wochenschrift - Aggressives Tumorwachstum, frühe Metastasierung und hohe Assoziation mit intensivem Nikotinkonsum sind die Charakteristika des kleinzelligen...     

Triazolam-induced changes in alcoholic thought processes

 This study was designed to examine and contrast cognitive effects (explicit memory and access to semantic knowledge) of the benzodiazepine Halcion (triazolam) in ten normal volunteers and ten cognitively unimpaired detoxified alcoholics. The two groups were indistinguishable from one another under placebo conditions on all measures of cognitive functioning. Under Halcion test conditions (0.375 mg PO), both groups were about equally impaired in their recall of to-be-remembered information. However, alcoholics, were more likely to recall information that they were not asked to remember (intrusion errors) on all measures of explicit remembering. Alcoholics also generated relatively uncommon (low frequency) responses from semantic memory, rather than common, categorically related associations in response to stimuli such as types of vegetables, flowers, and fruit following the administration of Halcion, but were not different from normal volunteers in the types of responses generated under placebo conditions. These findings suggest that a drug challenge that simulates many of the effects of acute alcohol administration induces alcoholics to think and remember differently (qualitatively) from normal volunteers. Received: 7 July 1997 / Final version: 22 September 1997     

Petit Mal-Grand Mal ECT: A Method to Induce Seizures Without Barbiturate Anesthesia

Petit mal-grand mal (PM-GM) electroconvulsive therapy (ECT) is a technique developed by Impastato to elicit unconsciousness with a subconvulsive electrical stimulus, rather than with barbiturate anesthesia. Muscle relaxation is produced with succinylcholine chloride before stimulus is applied. The cases reported here illustrate applications of the technique to depressed patients with severe cardiac and pulmonary disease, and the use of PM-GM ECT in a patient in whom seizures could not be elicited by the usual ECT technique is described.     

Schedule-dependency of in vivo modulation of 5-fluorouracil by leucovorin and uridine in murine colon carcinoma

Summary The effect of leucovorin (LV) given in various doses and schedules on the in vivo antitumor activity and toxicity of 5-fluorouracil (5FU) was studied in two murine colon cancer lines, i.e., Colon 26 (relatively resistant to 5FU) and Colon 38 (5FU sensitive), maintained in Balb-c and C57B1/6 mice, respectively. Mice were treated weekly with 5FU at the maximum tolerated dose, alone and in combination with LV. In Colon 26, neither simultaneous administration of 5FU and LV nor 5FU combined with delayed administration of LV potentiated the antitumor activity of 5FU. LV given twice — 1 hr before (50 mg/kg) and then together (50 mg/kg) with 5FU (100 mg/kg) — gave significantly better delay of tumor growth of both tumor lines than 5FU did alone (100 mg/kg). No differences were found after a total LV dose of 100 or 200 mg/kg. Delayed administration of uridine (3500 mg/kg) allowed the use of higher 5FU doses, which improved the antitumor effect on Colon 26. Systemic toxicity led to moderate weight loss in treated mice, but was comparable for mice treated with 5FU alone or combined with LV. Hematological toxicity consisted of moderate leukopenia (nadir 40%), which was observed with the most active schedule and was less severe than with 5FU alone. This schedule did not cause thrombocytopenia, but after discontinuation the thrombocyte count showed an overshoot. Addition of uridine to this schedule reduced hematological toxicity only slightly. It is concluded that LV potentiated the antitumor activity of 5FU against two solid tumor lines, i.e., a relatively resistant and a sensitive murine colon carcinoma, and that toxicity was moderate.Abbreviations 5FU 5-fluorouracil - LV leucovorin (folinic acid, 5-formyl-tetrahydrofolate) - FdUMP 5-fluoro 2-deoxyuridine 5monophosphate - TS thymidylate synthase - CH2-THF 5-10 methylenetetrahydrofolate - UR uridine - GDF growth delay factor - TD tumor doubling time - MTD maximum tolerated dose - T/C mean tumor volume of treated mice divided by mean tumor volume of control mice